{"title":"O-GlcNAcase regulates pluripotency states of human embryonic stem cells.","authors":"Qianyu Liu, Cheng Chen, Zhiya Fan, Honghai Song, Yutong Sha, Liyang Yu, Yingjie Wang, Weijie Qin, Wen Yi","doi":"10.1016/j.stemcr.2024.05.009","DOIUrl":"10.1016/j.stemcr.2024.05.009","url":null,"abstract":"<p><p>Understanding the regulation of human embryonic stem cells (hESCs) pluripotency is critical to advance the field of developmental biology and regenerative medicine. Despite the recent progress, molecular events regulating hESC pluripotency, especially the transition between naive and primed states, still remain unclear. Here we show that naive hESCs display lower levels of O-linked N-acetylglucosamine (O-GlcNAcylation) than primed hESCs. O-GlcNAcase (OGA), the key enzyme catalyzing the removal of O-GlcNAc from proteins, is highly expressed in naive hESCs and is important for naive pluripotency. Depletion of OGA accelerates naive-to-primed pluripotency transition. OGA is transcriptionally regulated by EP300 and acts as a transcription regulator of genes important for maintaining naive pluripotency. Moreover, we profile protein O-GlcNAcylation of the two pluripotency states by quantitative proteomics. Together, this study identifies OGA as an important factor of naive pluripotency in hESCs and suggests that O-GlcNAcylation has a broad effect on hESCs homeostasis.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-07-09Epub Date: 2024-06-27DOI: 10.1016/j.stemcr.2024.06.001
Meri Vattulainen, Jos G A Smits, Julian A Arts, Dulce Lima Cunha, Tanja Ilmarinen, Heli Skottman, Huiqing Zhou
{"title":"Deciphering the heterogeneity of differentiating hPSC-derived corneal limbal stem cells through single-cell RNA sequencing.","authors":"Meri Vattulainen, Jos G A Smits, Julian A Arts, Dulce Lima Cunha, Tanja Ilmarinen, Heli Skottman, Huiqing Zhou","doi":"10.1016/j.stemcr.2024.06.001","DOIUrl":"10.1016/j.stemcr.2024.06.001","url":null,"abstract":"<p><p>A comprehensive understanding of the human pluripotent stem cell (hPSC) differentiation process stands as a prerequisite for the development of hPSC-based therapeutics. In this study, single-cell RNA sequencing (scRNA-seq) was performed to decipher the heterogeneity during differentiation of three hPSC lines toward corneal limbal stem cells (LSCs). The scRNA-seq data revealed nine clusters encompassing the entire differentiation process, among which five followed the anticipated differentiation path of LSCs. The remaining four clusters were previously undescribed cell states that were annotated as either mesodermal-like or undifferentiated subpopulations, and their prevalence was hPSC line dependent. Distinct cluster-specific marker genes identified in this study were confirmed by immunofluorescence analysis and employed to purify hPSC-derived LSCs, which effectively minimized the variation in the line-dependent differentiation efficiency. In summary, scRNA-seq offered molecular insights into the heterogeneity of hPSC-LSC differentiation, allowing a data-driven strategy for consistent and robust generation of LSCs, essential for future advancement toward clinical translation.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-07-09Epub Date: 2024-06-27DOI: 10.1016/j.stemcr.2024.05.010
Nina Sofi Funa, Heidi Katharina Mjoseng, Kristian Honnens de Lichtenberg, Silvia Raineri, Deniz Esen, Anuska la Rosa Egeskov-Madsen, Roberto Quaranta, Mette Christine Jørgensen, Maria Skjøtt Hansen, Jonas van Cuyl Kuylenstierna, Kim Bak Jensen, Yi Miao, K Christopher Garcia, Philip A Seymour, Palle Serup
{"title":"TGF-β modulates cell fate in human ES cell-derived foregut endoderm by inhibiting Wnt and BMP signaling.","authors":"Nina Sofi Funa, Heidi Katharina Mjoseng, Kristian Honnens de Lichtenberg, Silvia Raineri, Deniz Esen, Anuska la Rosa Egeskov-Madsen, Roberto Quaranta, Mette Christine Jørgensen, Maria Skjøtt Hansen, Jonas van Cuyl Kuylenstierna, Kim Bak Jensen, Yi Miao, K Christopher Garcia, Philip A Seymour, Palle Serup","doi":"10.1016/j.stemcr.2024.05.010","DOIUrl":"10.1016/j.stemcr.2024.05.010","url":null,"abstract":"<p><p>Genetic differences between pluripotent stem cell lines cause variable activity of extracellular signaling pathways, limiting reproducibility of directed differentiation protocols. Here we used human embryonic stem cells (hESCs) to interrogate how exogenous factors modulate endogenous signaling events during specification of foregut endoderm lineages. We find that transforming growth factor β1 (TGF-β1) activates a putative human OTX2/LHX1 gene regulatory network which promotes anterior fate by antagonizing endogenous Wnt signaling. In contrast to Porcupine inhibition, TGF-β1 effects cannot be reversed by exogenous Wnt ligands, suggesting that induction of SHISA proteins and intracellular accumulation of Fzd receptors render TGF-β1-treated cells refractory to Wnt signaling. Subsequently, TGF-β1-mediated inhibition of BMP and Wnt signaling suppresses liver fate and promotes pancreas fate. Furthermore, combined TGF-β1 treatment and Wnt inhibition during pancreatic specification reproducibly and robustly enhance INSULIN<sup>+</sup> cell yield across hESC lines. This modification of widely used differentiation protocols will enhance pancreatic β cell yield for cell-based therapeutic applications.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-07-09Epub Date: 2024-06-13DOI: 10.1016/j.stemcr.2024.05.008
Jakub Scaber, Iona Thomas-Wright, Alex J Clark, Yinyan Xu, Björn F Vahsen, Mireia Carcolé, Ruxandra Dafinca, Lucy Farrimond, Adrian M Isaacs, David L Bennett, Kevin Talbot
{"title":"Cellular and axonal transport phenotypes due to the C9ORF72 HRE in iPSC motor and sensory neurons.","authors":"Jakub Scaber, Iona Thomas-Wright, Alex J Clark, Yinyan Xu, Björn F Vahsen, Mireia Carcolé, Ruxandra Dafinca, Lucy Farrimond, Adrian M Isaacs, David L Bennett, Kevin Talbot","doi":"10.1016/j.stemcr.2024.05.008","DOIUrl":"10.1016/j.stemcr.2024.05.008","url":null,"abstract":"<p><p>Induced pluripotent stem cell (iPSC)-derived motor neurons (MNs) from patients with amyotrophic lateral sclerosis (ALS) and the C9ORF72 hexanucleotide repeat expansion (HRE) have multiple cellular phenotypes, but which of these accurately reflect the biology underlying the cell-specific vulnerability of ALS is uncertain. We therefore compared phenotypes due to the C9ORF72 HRE in MNs with sensory neurons (SNs), which are relatively spared in ALS. The iPSC models were able to partially reproduce the differential gene expression seen between adult SNs and MNs. We demonstrated that the typical hallmarks of C9ORF72-ALS, including RNA foci and dipeptide formation, as well as specific axonal transport defects, occurred equally in MNs and SNs, suggesting that these in vitro phenotypes are not sufficient to explain the cell-type selectivity of ALS in isolation.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-07-02DOI: 10.1016/j.stemcr.2024.06.007
David Pamies, Jason Ekert, Marie-Gabrielle Zurich, Olivier Frey, Sophie Werner, Monica Piergiovanni, Benjamin S Freedman, Adrian Kee Keong Teo, Hendrik Erfurth, Darwin R Reyes, Peter Loskill, Pelin Candarlioglu, Laura Suter-Dick, Shan Wang, Thomas Hartung, Sandra Coecke, Glyn N Stacey, Beren Atac Wagegg, Eva-Maria Dehne, Francesca Pistollato, Marcel Leist
{"title":"Recommendations on fit-for-purpose criteria to establish quality management for microphysiological systems and for monitoring their reproducibility.","authors":"David Pamies, Jason Ekert, Marie-Gabrielle Zurich, Olivier Frey, Sophie Werner, Monica Piergiovanni, Benjamin S Freedman, Adrian Kee Keong Teo, Hendrik Erfurth, Darwin R Reyes, Peter Loskill, Pelin Candarlioglu, Laura Suter-Dick, Shan Wang, Thomas Hartung, Sandra Coecke, Glyn N Stacey, Beren Atac Wagegg, Eva-Maria Dehne, Francesca Pistollato, Marcel Leist","doi":"10.1016/j.stemcr.2024.06.007","DOIUrl":"10.1016/j.stemcr.2024.06.007","url":null,"abstract":"","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11252524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-06-11DOI: 10.1016/j.stemcr.2024.05.007
{"title":"Year in review: 2023 to 2024.","authors":"","doi":"10.1016/j.stemcr.2024.05.007","DOIUrl":"https://doi.org/10.1016/j.stemcr.2024.05.007","url":null,"abstract":"","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-06-11Epub Date: 2024-05-23DOI: 10.1016/j.stemcr.2024.04.012
Jarny Choi, Suzanne K Butcher, Paul W Angel, Jack Bransfield, Jake Barry, Noel Faux, Bobbie Shaban, Priyanka Pillai, Aleks Michalewicz, Christine A Wells
{"title":"Stemformatics data portal enables transcriptional benchmarking of lab-derived myeloid cells.","authors":"Jarny Choi, Suzanne K Butcher, Paul W Angel, Jack Bransfield, Jake Barry, Noel Faux, Bobbie Shaban, Priyanka Pillai, Aleks Michalewicz, Christine A Wells","doi":"10.1016/j.stemcr.2024.04.012","DOIUrl":"10.1016/j.stemcr.2024.04.012","url":null,"abstract":"<p><p>Stemformatics.org has been serving the stem cell research community for over a decade, by making it easy for users to find and view transcriptional profiles of pluripotent and adult stem cells and their progeny, comparing data derived from multiple tissues and derivation methods. In recent years, Stemformatics has shifted its focus from curation to collation and integration of public data with shared phenotypes. It now hosts several integrated expression atlases based on human myeloid cells, which allow for easy cross-dataset comparisons and discovery of emerging cell subsets and activation properties. The atlases are designed for external users to benchmark their own data against a common reference. Here, we use case studies to illustrate how to find and explore previously published datasets of relevance and how in-vitro-derived cells can be transcriptionally matched to cells in the integrated atlas to highlight phenotypes of interest.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11391030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-06-11Epub Date: 2024-05-16DOI: 10.1016/j.stemcr.2024.04.009
Qian Chen, Hiroyuki Hirai, Manwai Chan, Jilei Zhang, Minsu Cho, Scott H Randell, Preetish Kadur Lakshminarasimha Murthy, Jalees Rehman, Yuru Liu
{"title":"Characterization of perivascular alveolar epithelial stem cells and their niche in lung homeostasis and cancer.","authors":"Qian Chen, Hiroyuki Hirai, Manwai Chan, Jilei Zhang, Minsu Cho, Scott H Randell, Preetish Kadur Lakshminarasimha Murthy, Jalees Rehman, Yuru Liu","doi":"10.1016/j.stemcr.2024.04.009","DOIUrl":"10.1016/j.stemcr.2024.04.009","url":null,"abstract":"<p><p>Lung alveolar structure and function are maintained by subsets of alveolar type II stem cells (AT2s), but there is a need for characterization of these subsets and their associated niches. Here, we report a CD44<sup>high</sup> subpopulation of AT2s characterized by increased expression of genes that regulate immune signaling even during steady-state homeostasis. Disruption of one of these immune regulatory transcription factor STAT1 impaired the stem cell function of AT2s. CD44<sup>high</sup> cells were preferentially located near macro- blood vessels and a supportive niche constituted by LYVE1<sup>+</sup> endothelial cells, adventitial fibroblasts, and accumulated hyaluronan. In this microenvironment, CD44<sup>high</sup> AT2 cells were more responsive to transformation by KRAS than general AT2 cells. Moreover, after bacterial lung injury, there was a significant increase of CD44<sup>high</sup> AT2s and niche components distributed throughout the lung parenchyma. Taken together, CD44<sup>high</sup> AT2 cells and their perivascular niche regulate tissue homeostasis and tumor formation.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11390684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-06-11Epub Date: 2024-05-09DOI: 10.1016/j.stemcr.2024.04.007
Victor L Perez, Hazem M Mousa, Kiyoharu J Miyagishima, Amberlynn A Reed, An-Jey A Su, Thomas N Greenwell, Kia M Washington
{"title":"Retinal transplant immunology and advancements.","authors":"Victor L Perez, Hazem M Mousa, Kiyoharu J Miyagishima, Amberlynn A Reed, An-Jey A Su, Thomas N Greenwell, Kia M Washington","doi":"10.1016/j.stemcr.2024.04.007","DOIUrl":"10.1016/j.stemcr.2024.04.007","url":null,"abstract":"<p><p>Several gaps and barriers remain for transplanting stem cells into the eye to treat ocular disease, especially diseases of the retina. While the eye has historically been considered immune privileged, recent thinking has identified the immune system as both a barrier and an opportunity for eye stem cell transplantation. Recent approaches leveraging scaffolds or cloaking have been considered in other tissues beyond immune suppression. This perspective paper outlines approaches for transplantation and proposes opportunities to overcome barriers of the immune system in stem cell transplantation in the eye.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140905092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2024-06-11Epub Date: 2024-05-16DOI: 10.1016/j.stemcr.2024.04.008
Soraya O Sandoval, Gerarda Cappuccio, Karina Kruth, Sivan Osenberg, Saleh M Khalil, Natasha M Méndez-Albelo, Krishnan Padmanabhan, Daifeng Wang, Mark J Niciu, Anita Bhattacharyya, Jason L Stein, André M M Sousa, Elisa A Waxman, Elizabeth D Buttermore, Dosh Whye, Carissa L Sirois, Aislinn Williams, Mirjana Maletic-Savatic, Xinyu Zhao
{"title":"Rigor and reproducibility in human brain organoid research: Where we are and where we need to go.","authors":"Soraya O Sandoval, Gerarda Cappuccio, Karina Kruth, Sivan Osenberg, Saleh M Khalil, Natasha M Méndez-Albelo, Krishnan Padmanabhan, Daifeng Wang, Mark J Niciu, Anita Bhattacharyya, Jason L Stein, André M M Sousa, Elisa A Waxman, Elizabeth D Buttermore, Dosh Whye, Carissa L Sirois, Aislinn Williams, Mirjana Maletic-Savatic, Xinyu Zhao","doi":"10.1016/j.stemcr.2024.04.008","DOIUrl":"10.1016/j.stemcr.2024.04.008","url":null,"abstract":"<p><p>Human brain organoid models have emerged as a promising tool for studying human brain development and function. These models preserve human genetics and recapitulate some aspects of human brain development, while facilitating manipulation in an in vitro setting. Despite their potential to transform biology and medicine, concerns persist about their fidelity. To fully harness their potential, it is imperative to establish reliable analytic methods, ensuring rigor and reproducibility. Here, we review current analytical platforms used to characterize human forebrain cortical organoids, highlight challenges, and propose recommendations for future studies to achieve greater precision and uniformity across laboratories.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":null,"pages":null},"PeriodicalIF":5.9,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140959579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}